OP0219 INCIDENCE OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH JAK-INHIBITORS COMPARED TO BDMARDS: DATA FROM AN INTERNATIONAL COLLABORATION OF REGISTRIES (THE “JAK-POT” STUDY)
Authors: R. Aymon, D. Mongin, S. A. Bergstra, D. Choquette, C. Codreanu, R. L. Cordtz, D. C. Diederik, L. Dreyer, O. Elkayam, D. Huschek, K. Hyrich, F. Iannone, N. Inanc, L. Kearsley-Fleet, T. K. Kvien, B. Leeb, G. Lukina, D. Nordström, F. Onen, K. Pavelka, M. Pombo-Suarez, S. Aarrestad Provan, A. M. Rodrigues, Z. Rotar, A. Strangfeld, P. Verschueren, J. Zavada, D. Courvoisier, A. Finckh, K. Lauper
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Results of the "ORAL Surveillance" trial showed higher risk of major adverse cardiovascular (CV) events (MACE) for Janus kinase inhibitors (JAKi) than for TNF-inhibitors (TNFi). Currently, there is limited evidence of the real-world cardiovascular safety of JAKi. <h3>Objectives</h3> To assess the incidence of MACE in rheumatoid arthritis (RA) patients treated with JAKi, compared to other biologic agents in a large multi-country real-world population. <h3>Methods</h3> Patients from 14 RA registers from across Europe, Turkey and Québec (Canada), starting JAKi, TNF-inhibitors or bDMARDs with other modes of action (OMA), were included. MACE comprised strokes, myocardial infarctions and transient ischemic attacks and were attributed to a treatment up to 3 months after treatment cessation (except for rituximab for which it was 1 year), loss of follow-up, death or end of study. Incidence rates (IR) of MACE per 1000 patient-years (PY) with 95% confidence intervals (CI) were computed. Poisson regression, with propensity score weighting (including country, disease-, and patient-characteristics, and comorbidities, see Figure 1), was used to obtain adjusted incidence rate ratios (IRR), with 95% CI. A sub-analysis was performed on patients aged ≥ 50 years and ≥ 1 CV risk factor, mimicking the "ORAL Surveillance" trial inclusion criteria (RCT-duplicate cohort). <h3>Results</h3> Over the 50'325 treatment initiations considered (Table 1) in 34'932 patients with a mean follow-up of 2.8 years, 182 incident MACE were reported. Crude incidence was higher for OMA (2.63/1000 PY) than for JAKi (1.76/1000 PY) and TNFi (1.86/1000 PY). The adjusted Poisson regression demonstrated no significant difference in the incidence of MACE between JAKi vs TNFi (IRR = 0.87 (95% CI 0.56; 1.35)), and OMA vs TNFi (IRR = 1.05 (95% CI 0.74; 1.49)) (Figure 1). The RCT-duplicate cohort accounted for 38.4% of treatment courses and had a higher incidence of MACE in each treatment group (OMA: 3.75/1000 PY, JAKi: 2.65/1000 PY, TNFi: 3.48/1000 PY). Similarly to the overall population, no significant difference in the incidence of MACE was observed between JAKi vs TNFi (IRR = 0.78 (95% CI 0.44; 1.38)), and OMA vs TNFi (IRR = 0.84 (95% CI 0.53; 1.32)). <h3>Conclusion</h3> In this real-world study, including 14 RA registers and all currently available JAKi in the respective countries, we did not find a significantly higher risk of MACE in RA patients treated with JAKi compared to TNFi. Inclusion of other registers to increase the statistical power and the evaluation of other adverse events such as thromboembolic events, cancers and serious infections are planned. <h3>References</h3> [1]Ann Rheum Dis 2022. doi: 10.1136/annrheumdis-2021-221915. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Romain Aymon: None declared, Denis Mongin: None declared, Sytske Anne Bergstra Grant/research support from: Pfizer, Denis Choquette Speakers bureau: Abbvie, Amgen, Pizer, Sandoz and Tevapharm, Consultant of: Abbvie, Amgen, Celltrion, Eli Lilly, Fresenius-Kabi, INESSS, Jamppharma, Pfizer, Sandoz and Tevapharm, Grant/research support from: Rhumadata is supported through grants from Abbvie, Amgen, Fresenius-Kabi, Eli Lilly, Pfizer, Sandoz and Tevapharm, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, René Lindholm Cordtz: None declared, De Cock Diederik: None declared, Lene Dreyer Grant/research support from: Research grant from BMS outside the present work, Ori Elkayam Consultant of: Pfizer, Lilly, Abbvie, Novartis, Jansen, BI, Doreen Huschek: None declared, Kimme Hyrich Speakers bureau: Abbvie, Grant/research support from: Pfizer and BMS, Florenzo Iannone Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, Nevsun Inanc Speakers bureau: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, MSD, Boehringer Ingelheim and Abdi İbrahim, Consultant of: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, MSD, Boehringer Ingelheim and Abdi İbrahim, Lianne Kearsley-Fleet: None declared, Tore K. Kvien Speakers bureau: AbbVie, Amgen, Celltrion, Gilead, Grünenthal, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Grünenthal, Novartis, Pfizer, Sandoz, UCB, Burkhard Leeb Speakers bureau: Eli-Lilly, Pfizer, Astropharma, Biogen, Celgene, Consultant of: Eli-Lilly, Pfizer, AbbVie, Biogen, Celgene, Galina Lukina Speakers bureau: AbbVie, Pfizer, Novartis, Dan Nordström Consultant of: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Fatos Onen Speakers bureau: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, and MSD, Consultant of: Abbvie, Amgen, Pfizer, Novartis, Roche, Lilly, and MSD, Karel Pavelka Speakers bureau: Novartis, AbbVie, Eli Lilly, Pfizer, UCB, MSD, Biogen, Celltrion, Manuel Pombo-Suarez Speakers bureau: Janssen, Merck Sharp &amp; Dohme, Novartis and Sanofi Genzyme, Consultant of: Janssen, Merck Sharp &amp; Dohme, Novartis and Sanofi Genzyme, Sella Aarrestad Provan: None declared, Ana Maria Rodrigues Speakers bureau: Amgen, Phizer, Astrazeneca, Novartis, Roche and Nordic pharma, Consultant of: Amgen, Phizer, Astrazeneca, Novartis, Roche and Nordic pharma, Grant/research support from: Reuma.pt is supported througth grants from Abbvie, Bristol Myers Squibb, Lilly, MSD, Novartis, Pfizer, Boehringer Ingelheim, Astrazeneca and Amgen, Ziga Rotar Speakers bureau: Abbive, Amgen, Biogen, Eli Lilly, Medis, Mediasi, Novartis, Sandoz, Pfizer, MSD, Sanofi, Roche, SOBI., Consultant of: Abbive, Amgen, Biogen, Eli Lilly, Medis, Mediasi, Novartis, Sandoz, Pfizer, MSD, Sanofi, Roche, SOBI., Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB, Grant/research support from: Non-personal, joint grant from a consortium of 14 pharmaceutical companies for the biologics register RABBIT to my institute., Patrick Verschueren Speakers bureau: Abbvie, Eli Lilly, Galapagos, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma and Sidekick Health, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Delphine Courvoisier: None declared, Axel Finckh Consultant of: Pfizer, BMS, MSD, Eli-Lilly, AbbVie, Galapagos, Mylan, UCB, Viatris, Grant/research support from: Pfizer INC, AbbVie, Galapagos, Eli Lilly, Kim Lauper Speakers bureau: Pfizer, Viatris and Celltrion, Consultant of: Pfizer.